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Lieberman NAP, Lin MJ, Xie H, et al. Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar. PLoS Negl Trop Dis. 2021;15(12):e0010063doi: 10.1371/journal.pntd.0010063.
Lieberman, N. A. P., Lin, M. J., Xie, H., Shrestha, L., Nguyen, T., Huang, M. L., Haynes, A. M., Romeis, E., Wang, Q. Q., Zhang, R. L., Kou, C. X., Ciccarese, G., Dal Conte, I., Cusini, M., Drago, F., Nakayama, S. I., Lee, K., Ohnishi, M., Konda, K. A., Vargas, S. K., Eguiluz, M., Caceres, C. F., Klausner, J. D., Mitjà, O., Rompalo, A., Mulcahy, F., Hook, E. W., Lukehart, S. A., Casto, A. M., Roychoudhury, P., DiMaio, F., Giacani, L., & Greninger, A. L. (2021). Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar. PLoS neglected tropical diseases, 15(12), e0010063. https://doi.org/10.1371/journal.pntd.0010063
Lieberman, Nicole A P, et al. "Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar." PLoS neglected tropical diseases vol. 15,12 (2021): e0010063. doi: https://doi.org/10.1371/journal.pntd.0010063
Lieberman NAP, Lin MJ, Xie H, Shrestha L, Nguyen T, Huang ML, Haynes AM, Romeis E, Wang QQ, Zhang RL, Kou CX, Ciccarese G, Dal Conte I, Cusini M, Drago F, Nakayama SI, Lee K, Ohnishi M, Konda KA, Vargas SK, Eguiluz M, Caceres CF, Klausner JD, Mitjà O, Rompalo A, Mulcahy F, Hook EW, Lukehart SA, Casto AM, Roychoudhury P, DiMaio F, Giacani L, Greninger AL. Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar. PLoS Negl Trop Dis. 2021 Dec 22;15(12):e0010063. doi: 10.1371/journal.pntd.0010063. eCollection 2021 Dec. PMID: 34936652; PMCID: PMC8735616.
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PLoS Negl Trop Dis. 2021 Dec 22;15(12):e0010063. doi: 10.1371/journal.pntd.0010063. eCollection 2021 Dec.

Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar.

PLoS neglected tropical diseases

Nicole A P Lieberman, Michelle J Lin, Hong Xie, Lasata Shrestha, Tien Nguyen, Meei-Li Huang, Austin M Haynes, Emily Romeis, Qian-Qiu Wang, Rui-Li Zhang, Cai-Xia Kou, Giulia Ciccarese, Ivano Dal Conte, Marco Cusini, Francesco Drago, Shu-Ichi Nakayama, Kenichi Lee, Makoto Ohnishi, Kelika A Konda, Silver K Vargas, Maria Eguiluz, Carlos F Caceres, Jeffrey D Klausner, Oriol Mitjà, Anne Rompalo, Fiona Mulcahy, Edward W Hook, Sheila A Lukehart, Amanda M Casto, Pavitra Roychoudhury, Frank DiMaio, Lorenzo Giacani, Alexander L Greninger

Affiliations

  1. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, United States of America.
  2. Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, United States of America.
  3. Institute of Dermatology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
  4. National Center for STD Control, China Centers for Disease Control and Prevention, Nanjing, China.
  5. Department of Dermatology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  6. Health Sciences Department, Section of Dermatology, San Martino University Hospital, Genoa, Italy.
  7. STI Clinic, Infectious Diseases Unit, University of Turin, Turin, Italy.
  8. Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
  9. Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.
  10. Unit of Health, Sexuality and Human Development and Laboratory of Sexual Health, Universidad Peruana Cayetano-Heredia, Lima, Peru.
  11. Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
  12. Fight Aids and Infectious Diseases Foundation, Hospital Germans Trias i Pujol, Barcelona, Spain.
  13. Lihir Medical Centre-International SOS, Newcrest Mining, Lihir Island, Papua New Guinea.
  14. Department of Infectious Diseases, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
  15. Department of Genito Urinary Medicine and Infectious Diseases, St James's Hospital, Dublin, Ireland.
  16. Department of Medicine, University of Alabama, Birmingham, Birmingham, Alabama, United States of America.
  17. Department of Global Health, University of Washington, Seattle, Washington, United States of America.
  18. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  19. Department of Biochemistry, University of Washington, Seattle, Washington, United States of America.

PMID: 34936652 PMCID: PMC8735616 DOI: 10.1371/journal.pntd.0010063

Abstract

In spite of its immutable susceptibility to penicillin, Treponema pallidum (T. pallidum) subsp. pallidum continues to cause millions of cases of syphilis each year worldwide, resulting in significant morbidity and mortality and underscoring the urgency of developing an effective vaccine to curtail the spread of the infection. Several technical challenges, including absence of an in vitro culture system until very recently, have hampered efforts to catalog the diversity of strains collected worldwide. Here, we provide near-complete genomes from 196 T. pallidum strains-including 191 T. pallidum subsp. pallidum-sequenced directly from patient samples collected from 8 countries and 6 continents. Maximum likelihood phylogeny revealed that samples from most sites were predominantly SS14 clade. However, 99% (84/85) of the samples from Madagascar formed two of the five distinct Nichols subclades. Although recombination was uncommon in the evolution of modern circulating strains, we found multiple putative recombination events between T. pallidum subsp. pallidum and subsp. endemicum, shaping the genomes of several subclades. Temporal analysis dated the most recent common ancestor of Nichols and SS14 clades to 1717 (95% HPD: 1543-1869), in agreement with other recent studies. Rates of SNP accumulation varied significantly among subclades, particularly among different Nichols subclades, and was associated in the Nichols A subclade with a C394F substitution in TP0380, a ERCC3-like DNA repair helicase. Our data highlight the role played by variation in genes encoding putative surface-exposed outer membrane proteins in defining separate lineages, and provide a critical resource for the design of broadly protective syphilis vaccines targeting surface antigens.

Conflict of interest statement

The authors have declared that no competing interests exist.

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